Structural Genomics Research

DNA is tightly packaged in the cell. Strands of DNA are wrapped around histone proteins to form nucleosomes, which coil to form chromatin. Chromatin is further condensed into chromosomes.

Credit: Darryl Leja, NHGRI

The study of structural genomics aims to complete the "parts list" of cancer, where "parts" are genetic structures – DNA and RNA– that are altered in cancer. Structural genomics research, such as The Cancer Genome Atlas (TCGA), has already revealed a variety of oncogenic alterations, and these discoveries have improved the care of patients with many different types of cancer.

Tools and Methods

CCG characterizes tumor samples and matched normal tissue using a variety of techniques because a deep and comprehensive study of the genome can provide significantly more information about cancer biology than any single platform can. CCG’s tools include:

The Genome Characterization Pipeline carries out CCG’s structural genomics research and the resulting data are made available via the Genomic Data Commons (GDC). Learn more about how CCG works and what data are produced.

Patients with these alterations receive standard of care treatment followed by a targeted therapy that corresponds to the alteration in their tumors’ genome, erlotinib for EGFRmutations and crizotinib for ALK rearrangements. ALCHEMIST is a collaboration between CCG and NCI’s Division of Cancer Treatment and Diagnosis.

CDDP aims to identify driver mutations in as few as 2% of patients. By sequencing a large number of cases, CDDP will have the statistical power to discover recurrent mutations in genes that may drive the oncogenic process. As a pilot project, CDDP will analyze samples from lung, colon, and ovarian cancers.

CTSP launched out of a joint aspiration of CCG and NCI’s Division of Cancer Treatment and Diagnosis (DCTD) to promote the use of genomics in NCI-sponsored clinical trials of the National Clinical Trials Network (NCTN). CTSP’s goal is to elucidate the molecular basis of response and resistance to therapies studied. The cancer types currently under study are breast cancer, renal cell carcinoma, and diffuse large B-cell lymphoma.

The EOMI, a collaboration between CCG and the Division of Cancer Prevention's NCI Community Oncology Research Program (NCORP), studies the molecular characteristics of six cancers that develop at an earlier age and may occur in higher rates and/or be more aggressive in some populations. By characterizing cancers from NCORP's minority/underserved sites, the initiative is investigating how biology may underpin these disparities.

The ER Initiative aims to understand the genetic basis of some cancer patients' dramatically positive responses to particular drug therapies that are not effective for most other patients. This pilot study is characterizing the genomic profiles of 100 "exceptional responder" patients who were treated for a variety of different types of cancer. The Exceptional Responders Initiative is a joint initiative of CCG and the Division of Cancer Treatment and Diagnosis (DCTD).

TCGA is a collaboration between the National Cancer Institute (NCI) and the National Human Genome Research Institute (NHGRI) that has generated comprehensive, multi-dimensional maps of the key genomic changes in 33 types of cancer. The TCGA dataset, comprising more than two petabytes of genomic data, is publically available and helps the cancer research community improve the prevention, diagnosis, and treatment of cancer.

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